Lentiviral vectors derived from the human immunodeficiency virus (notably HIV-1) are part of the vectors the most used for gene therapy. These vectors are generally pseudotyped with glycoproteins from other viruses: gibbon ape leukemia virus (GALV; GaLV-TR glycoproteins), vesicular stomatitis virus (VSV-g), or measles virus (MV). Processes for purifying clinical batches of lentiviral vectors pseudotyped with the VSV-G protein have been described (Schweizer and Merten, 2010). However, viral vectors pseudotyped with other envelope proteins, and more particularly with glycoproteins derived from GaLV or MV, are not widely used since no satisfactory purifying protocol is available at the present time. The major limiting obstacle for the purification of this type of pseudotyped vectors is related to the instability and fragility of certain membrane glycoproteins. However, these vectors are of particular interest as regards their less broad tropism than that of vectors pseudotyped with the VSV-G protein. For example, the vectors pseudotyped with a glycoprotein derived from GALV have more restricted tropism and more particularly target hematopoietic stem cells. Making available an efficient process for purifying vectors pseudotyped with GALV glycoproteins therefore represents a major challenge in the field of gene therapy.
The inventors therefore proposed the development of a process for purifying enveloped viruses, and notably viruses pseudotyped with the envelope glycoprotein GaLV or by other envelope proteins, aiming at producing preparations of viruses for clinical use.